High Levels of Tumor Necrosis Factor-α Downregulate Antimicrobial Iron Transport Protein, Nramp1, in Chronic Hemodialysis Patients: A Key Factor for Infection Risk
High Levels of Tumor Necrosis Factor-α Downregulate Antimicrobial Iron Transport Protein, Nramp1, in Chronic Hemodialysis Patients: A Key Factor for Infection Risk
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DOI：
10.1159/000337742
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发表时间：
2012-01-01
影响因子：
4.2
通讯作者：
Nakanishi, Takeshi
中科院分区：
文献类型：
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作者：
Moriguchi, Rintarou;Otaki, Yoshinaga;Nakanishi, Takeshi
背景/目的：维持性血液透析（MHD）患者对感染的易感性是死亡和发病的主要原因。天然耐药相关巨噬细胞蛋白1（Nramp 1）调节细胞内病原体增殖，其mRNA表达在多形核白细胞（PMNLs）中最高。本研究旨在探讨MHD患者PMNLs中Nramp 1的表达水平及其影响因素。方法：20例MHD患者和24例健康志愿者（对照组）。采用相对定量PCR检测Nramp 1 mRNA，采用实时定量PCR和Western blot分析或免疫组织化学方法半定量检测蛋白水平。还检测了肿瘤坏死因子-α（TNF-α）或白细胞介素-6（IL-6）对来自对照的PMNL中Nramp 1表达的影响。结果：MHD患者PMNLs中Nramp 1 mRNA和蛋白水平均显著低于对照组。MHD组的血清TNF-α水平显著升高，并与Nramp 1 mRNA水平呈负相关。在对照组的PMNLs中加入TNF-α可降低Nramp 1的mRNA和蛋白水平。IL-6对Nramp 1 mRNA和蛋白表达无明显影响。结论：我们发现Nramp 1在MHD患者的PMNL中下调，这构成了抵御细菌挑战的第一道防御屏障。高水平的TNF-α可能与Nramp 1的下调有关。我们的研究结果表明，在MHD患者中观察到的感染易感性可能部分是由于铁的细胞内处理和捐赠更多的铁细菌的损害。版权所有（C）2012 S. Karger AG，巴塞尔
Background/Aims: The susceptibility of patients on maintenance hemodialysis (MHD) to infections is a major cause of mortality and morbidity. Natural resistance-associated macrophage protein 1 (Nramp1) regulates intracellular pathogen proliferation, and its mRNA expression is highest in polymorphonuclear leukocytes (PMNLs). The purpose of this study was to determine the level of Nramp1 in PMNLs from MHD patients and the factors affecting its expression. Methods: Twenty MHD patients and 24 healthy volunteers (controls) were recruited. Relative quantitative PCR was used to measure Nramp1 mRNA, and protein levels were semiquantified by means of real-time PCR and Western blot analysis or immunohistochemistry. The effect of tumor necrosis factor-alpha (TNF-alpha) or interleukin-6 (IL-6) on Nramp1 expression in PMNLs from controls was also examined. Results: Nramp1 mRNA and protein levels were substantially lower in PMNLs from MHD than control subjects. Serum TNF-alpha levels were significantly higher in the MHD group and were inversely correlated with Nramp1 mRNA levels. The addition of TNF-alpha to PMNLs from control subjects decreased mRNA and protein levels of Nramp1. IL-6 did not alter Nramp1 mRNA or protein expression. Conclusion: We found that Nramp1 was downregulated in the PMNLs of MHD patients, which constitute the first defense barrier against bacterial challenges. High levels of TNF-alpha may be associated with the downregulation of Nramp1. Our findings indicate that the susceptibility to infection observed in MHD patients could be partly due to the impairment of the intracellular handling of iron and the donation of more iron to the bacteria. Copyright (C) 2012 S. Karger AG, Basel